Investigation of effects of pegylated doxorubicin and fluoxetine combination in experimental liver metastatic breast cancer mouse model

Objective: Triple-negative breast cancer is the most aggressive breast cancer subtype that has poor prognosis and limited effective treatment options due to the high metastasis potential. Drug resistance is a major therapeutic obstacle in metastatic triple-negative breast cancer treatment. In this thesis study, our objective was to investigate the synergistic effects of pegylated liposomal doxorubicin and fluoxetine in mice metastatic breast cancer model. Method: Female mice were inoculated into right mammary fat pad with 4TLM murine breast cancer liver metastasis cells. Mice were randomized into four groups: control (0.1 ml/day, serum physiologic), fluoxetine (0.4 mg/kg/day), pegylated liposomal doxorubicin (cumulative dose of 17.5 mg/kg) and pegylated liposomal doxorubicin (cumulative dose of 17.5 mg/kg) - fluoxetine (0.4 mg/kg/day) combination. Primary tumor volume was monitored by using vernier caliper during the treatment. Mice were sacrificed at the end of the 4th week. IL-6, IL-10, IL17A and IFN-gamma were measured in mix leukocyte culture supernatants by ELISA. Lung metastasis was evaluated macroscopically. Results: Primary tumor volume and number of lung metastasis decreased in groups treated with pegylated liposomal doxorubicin and pegylated liposomal doxorubicin-fluoxetine combination. Pegylated liposomal doxorubicin-fluoxetine treatment increased IL-10, IL17A and IFN-gamma levels, but decreased IL-6 levels. Conclusion: Pegylated liposomal doxorubicin and pegylated liposomal doxorubicin-fluoxetine treatments were found to be effective for primary tumor and lung metastasis. Cytokine levels was changed only by pegylated liposomal doxorubicin-fluoxetine combination. Pegylated liposomal doxorubicin-fluoxetine combination, could influence primary tumor and metastasis parameters in different doses. Key words: pegylated doxorubicin, fluoxetine, breast cancer